Medical Biology - Theses
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ItemEffects of Universal Iron Interventions on Intestinal Microbiota in Young Children: A Substudy of the BRISC Randomised Controlled Trial in Bangladesh( 2023-06)Infants and children in low- and middle-income countries (LMICs) face numerous health threats, including those related to infectious diseases and poor nutrition. Anaemia, highly prevalent among pre-school children in LMICs in South Asia and sub-Saharan Africa, is often attributed to iron deficiency. To reduce the global anaemia burden, the World Health Organization recommends universal iron interventions to children aged 6 months to 12 years in areas with a high prevalence of anaemia. However, studies examining the effects of iron on the intestinal microbiome have revealed pathogenic changes to bacterial composition and increased intestinal inflammation. The existing research lacks consistency in study design, including iron doses, formulations, and follow-up periods. There is therefore an urgent need for well conducted trials to assess the impact of iron interventions on the gut microbiome and determine their safety for use in children in LMICs. This thesis addresses this research question by investigating the effects of oral iron interventions on the gut microbiome of infants enrolled in the BRISC (Benefits and Risks of Iron Interventions in Children) Trial, a large, placebo-controlled randomised controlled trial in rural Bangladesh. A total of 3300 infants, aged eight months, were randomised to one of two oral iron groups or a placebo group for three months. Stool samples were collected at baseline (n=925), immediately post-intervention (n=809), and at nine-month follow-up (n=578) from a subgroup of these infants. The key finding from this analysis was that iron did not cause a pathogenic reprofiling of the gut microbiome at either post-intervention time point, nor were there sustained changes in subgroups stratified by baseline iron status. This indicates that universal iron interventions are safe with respect to the gut microbiome in this setting. During the trial there was a high incidence of community antibiotic use among the participants. Antibiotics are known to impact gut microbiota composition, leading to reduced diversity and potentially pathogenic changes to taxonomy, and in some studies these changes persisted for months. Furthermore, antibiotic use has been linked to increased antimicrobial resistance (AMR), posing a significant threat to global health. This thesis examines the effects of antibiotic use on bacterial composition and the development of AMR in the microbiome samples. Antibiotics in the week preceding sample collection were associated with reduced alpha diversity and increases in phylum Proteobacteria including genera Enterococcus and Escherichia/Shigella. They were also linked to an increase in three AMR genes known to be encoded by Enterococcus faecium. Earlier antibiotic use was not associated with taxonomic or AMR gene differences at this same sampling time point, suggesting that the changes due to antibiotic use may be transient in nature. Using a combination of sequencing techniques including shotgun metagenomics, this thesis addresses crucial research questions regarding the effects of iron interventions and antibiotic use on the gut microbiome of infants in LMICs. The findings contribute to our understanding of the iron-microbiome relationship and the impact of antibiotic use on microbiota composition and AMR development. These insights have significant implications for public health strategies aimed at improving health and developmental outcomes of children in LMICs.